Small extracellular vesicles derived from Nrf2-stimulated bone marrow mesenchymal stem cells ameliorated the testis damage and fertility disorder in doxorubicin-treated mice

IF 3.3 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology Pub Date : 2025-02-01 DOI:10.1016/j.reprotox.2025.108847

Maryam Taher, Hanieh Jalali, Homa Mohseni Kouchesfehani

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引用次数: 0

Abstract

Bone marrow mesenchymal/stromal stem cell (BMSC)-derived small extracellular vesicles (sEVs) are promising therapeutic agents owing to their low immunogenicity and ability to cross biological barriers. Doxorubicin (DOX), a common chemotherapeutic agent, damages testicular tissue. This study aimed to enhance the antioxidant activity of sEVs by activating the Nrf2 gene in BMSCs and evaluate their therapeutic potential for DOX-induced fertility disorders. Testicular damage was induced by DOX in NMRI mice. BMSCs from Wistar rats were treated with Bardoxolone methyl (BaMet) to upregulate Nrf2. The sEVs were isolated through differential ultracentrifugation and validated for size, morphology, and protein expression. The antioxidant activity was assessed using specific kits. sEVs containing 10 μg of proteins were injected intravenously into DOX-injured mice. After 35 days, the testes were collected for histopathological, hormonal, and immunological analyses, along with the evaluation of sperm parameters. Male and female mice were paired to determine the pregnancy rates. BaMet-sEVs exhibited higher antioxidant activity and significantly improved serum testosterone levels, testicular cell populations, sperm viability, and motility in DOX-injured mice. In addition, BaMet-sEVs treatment enhanced fertility and increased the number of offspring. This study demonstrated the effectiveness of BaMet-sEVs in mitigating DOX-induced testicular damage.

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来源期刊

Reproductive toxicology 生物-毒理学

CiteScore

6.50

自引率

3.00%

发文量

131

审稿时长

45 days

期刊介绍： Drawing from a large number of disciplines, Reproductive Toxicology publishes timely, original research on the influence of chemical and physical agents on reproduction. Written by and for obstetricians, pediatricians, embryologists, teratologists, geneticists, toxicologists, andrologists, and others interested in detecting potential reproductive hazards, the journal is a forum for communication among researchers and practitioners. Articles focus on the application of in vitro, animal and clinical research to the practice of clinical medicine. All aspects of reproduction are within the scope of Reproductive Toxicology, including the formation and maturation of male and female gametes, sexual function, the events surrounding the fusion of gametes and the development of the fertilized ovum, nourishment and transport of the conceptus within the genital tract, implantation, embryogenesis, intrauterine growth, placentation and placental function, parturition, lactation and neonatal survival. Adverse reproductive effects in males will be considered as significant as adverse effects occurring in females. To provide a balanced presentation of approaches, equal emphasis will be given to clinical and animal or in vitro work. Typical end points that will be studied by contributors include infertility, sexual dysfunction, spontaneous abortion, malformations, abnormal histogenesis, stillbirth, intrauterine growth retardation, prematurity, behavioral abnormalities, and perinatal mortality.